EP3297983B1 - Process for preparing a macrocyclic diketone - Google Patents
Process for preparing a macrocyclic diketone Download PDFInfo
- Publication number
- EP3297983B1 EP3297983B1 EP16723374.1A EP16723374A EP3297983B1 EP 3297983 B1 EP3297983 B1 EP 3297983B1 EP 16723374 A EP16723374 A EP 16723374A EP 3297983 B1 EP3297983 B1 EP 3297983B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- compound
- formula
- ruthenium
- oxidizing agent
- oxidation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
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- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 125000005594 diketone group Chemical group 0.000 title description 18
- 238000007254 oxidation reaction Methods 0.000 claims description 54
- 150000001875 compounds Chemical class 0.000 claims description 50
- 239000007800 oxidant agent Substances 0.000 claims description 48
- 150000003304 ruthenium compounds Chemical class 0.000 claims description 43
- 238000000034 method Methods 0.000 claims description 39
- 239000011541 reaction mixture Substances 0.000 claims description 39
- 230000003647 oxidation Effects 0.000 claims description 35
- 239000000243 solution Substances 0.000 claims description 19
- -1 diketone compound Chemical class 0.000 claims description 15
- 239000003960 organic solvent Substances 0.000 claims description 15
- 239000007864 aqueous solution Substances 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 13
- 239000012062 aqueous buffer Substances 0.000 claims description 9
- 239000006172 buffering agent Substances 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical group Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 claims description 8
- FRTDAFYYAIXLRJ-UHFFFAOYSA-N 3-methylcyclopentadecane-1,5-dione Chemical compound CC1CC(=O)CCCCCCCCCCC(=O)C1 FRTDAFYYAIXLRJ-UHFFFAOYSA-N 0.000 claims description 7
- HFVJJXVZEQUUNT-UHFFFAOYSA-N cyclopentadecane-1,5-dione Chemical compound O=C1CCCCCCCCCCC(=O)CCC1 HFVJJXVZEQUUNT-UHFFFAOYSA-N 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- GTCKPGDAPXUISX-UHFFFAOYSA-N ruthenium(3+);trinitrate Chemical class [Ru+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O GTCKPGDAPXUISX-UHFFFAOYSA-N 0.000 claims description 6
- 230000003197 catalytic effect Effects 0.000 claims description 5
- 229910052707 ruthenium Inorganic materials 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- ROZSPJBPUVWBHW-UHFFFAOYSA-N [Ru]=O Chemical class [Ru]=O ROZSPJBPUVWBHW-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 229910001925 ruthenium oxide Inorganic materials 0.000 claims description 4
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical group [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 238000012423 maintenance Methods 0.000 claims description 3
- 239000003791 organic solvent mixture Substances 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 description 55
- 229940099408 Oxidizing agent Drugs 0.000 description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 239000012074 organic phase Substances 0.000 description 24
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 23
- 239000012071 phase Substances 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 15
- 239000003054 catalyst Substances 0.000 description 11
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 229910001927 ruthenium tetroxide Inorganic materials 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 9
- 239000007789 gas Substances 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 229910019891 RuCl3 Inorganic materials 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000007853 buffer solution Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 150000003303 ruthenium Chemical class 0.000 description 6
- WOCIAKWEIIZHES-UHFFFAOYSA-N ruthenium(iv) oxide Chemical compound O=[Ru]=O WOCIAKWEIIZHES-UHFFFAOYSA-N 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 5
- 239000011261 inert gas Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 238000010626 work up procedure Methods 0.000 description 5
- XTEGARKTQYYJKE-UHFFFAOYSA-M Chlorate Chemical class [O-]Cl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-M 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 description 4
- 239000011707 mineral Substances 0.000 description 4
- 235000010755 mineral Nutrition 0.000 description 4
- 125000004430 oxygen atom Chemical group O* 0.000 description 4
- 239000005708 Sodium hypochlorite Substances 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 125000005907 alkyl ester group Chemical class 0.000 description 3
- QBWCMBCROVPCKQ-UHFFFAOYSA-N chlorous acid Chemical class OCl=O QBWCMBCROVPCKQ-UHFFFAOYSA-N 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 239000011736 potassium bicarbonate Substances 0.000 description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- WYRXRHOISWEUST-UHFFFAOYSA-K ruthenium(3+);tribromide Chemical compound [Br-].[Br-].[Br-].[Ru+3] WYRXRHOISWEUST-UHFFFAOYSA-K 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 3
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- SXVPOSFURRDKBO-UHFFFAOYSA-N Cyclododecanone Chemical compound O=C1CCCCCCCCCCC1 SXVPOSFURRDKBO-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 229910021603 Ruthenium iodide Inorganic materials 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229950005499 carbon tetrachloride Drugs 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- XMFOQHDPRMAJNU-UHFFFAOYSA-N lead(II,IV) oxide Inorganic materials O1[Pb]O[Pb]11O[Pb]O1 XMFOQHDPRMAJNU-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 238000005949 ozonolysis reaction Methods 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 238000007539 photo-oxidation reaction Methods 0.000 description 2
- 229960003975 potassium Drugs 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000012286 potassium permanganate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229940090181 propyl acetate Drugs 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- LJZVDOUZSMHXJH-UHFFFAOYSA-K ruthenium(3+);triiodide Chemical compound [Ru+3].[I-].[I-].[I-] LJZVDOUZSMHXJH-UHFFFAOYSA-K 0.000 description 2
- IREVRWRNACELSM-UHFFFAOYSA-J ruthenium(4+);tetrachloride Chemical compound Cl[Ru](Cl)(Cl)Cl IREVRWRNACELSM-UHFFFAOYSA-J 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- 150000003738 xylenes Chemical class 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- IOCRTZHWGSGNLY-UHFFFAOYSA-N 2,3,4,5,6,7,8,9,10,11,12,13-dodecahydro-1H-cyclopenta[12]annulene-3a,13a-diol Chemical compound C12(CCCCCCCCCCC2(CCC1)O)O IOCRTZHWGSGNLY-UHFFFAOYSA-N 0.000 description 1
- LVDMPQMSBKURLS-UHFFFAOYSA-J 2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate;ruthenium(4+) Chemical compound [Ru+4].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O LVDMPQMSBKURLS-UHFFFAOYSA-J 0.000 description 1
- QLLXYZZGHARQKA-UHFFFAOYSA-N 2-methyl-2,3,4,5,6,7,8,9,10,11,12,13-dodecahydro-1H-cyclopenta[12]annulene-3a,13a-diol Chemical compound CC1CC2(CCCCCCCCCCC2(C1)O)O QLLXYZZGHARQKA-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- ZKQDCIXGCQPQNV-UHFFFAOYSA-N Calcium hypochlorite Chemical compound [Ca+2].Cl[O-].Cl[O-] ZKQDCIXGCQPQNV-UHFFFAOYSA-N 0.000 description 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 1
- 241000402754 Erythranthe moschata Species 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- BJIOGJUNALELMI-ONEGZZNKSA-N Isoeugenol Natural products COC1=CC(\C=C\C)=CC=C1O BJIOGJUNALELMI-ONEGZZNKSA-N 0.000 description 1
- ALHUZKCOMYUFRB-OAHLLOKOSA-N Muscone Chemical compound C[C@@H]1CCCCCCCCCCCCC(=O)C1 ALHUZKCOMYUFRB-OAHLLOKOSA-N 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 239000012080 ambient air Substances 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000003118 aryl group Chemical class 0.000 description 1
- FLNKWZNWHZDGRT-UHFFFAOYSA-N azane;dihydrochloride Chemical compound [NH4+].[NH4+].[Cl-].[Cl-] FLNKWZNWHZDGRT-UHFFFAOYSA-N 0.000 description 1
- GBDZMMXUOBAJMN-UHFFFAOYSA-K azane;ruthenium(3+);trichloride Chemical compound N.N.N.N.N.N.[Cl-].[Cl-].[Cl-].[Ru+3] GBDZMMXUOBAJMN-UHFFFAOYSA-K 0.000 description 1
- HPEWZLCIOKVLBZ-UHFFFAOYSA-N barium hypochlorite Chemical compound [Ba+2].Cl[O-].Cl[O-] HPEWZLCIOKVLBZ-UHFFFAOYSA-N 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 235000010338 boric acid Nutrition 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 231100000481 chemical toxicant Toxicity 0.000 description 1
- OSVXSBDYLRYLIG-UHFFFAOYSA-N chlorine dioxide Inorganic materials O=Cl=O OSVXSBDYLRYLIG-UHFFFAOYSA-N 0.000 description 1
- 229910001914 chlorine tetroxide Inorganic materials 0.000 description 1
- TVWHTOUAJSGEKT-UHFFFAOYSA-N chlorine trioxide Chemical compound [O]Cl(=O)=O TVWHTOUAJSGEKT-UHFFFAOYSA-N 0.000 description 1
- QBWCMBCROVPCKQ-UHFFFAOYSA-M chlorite Chemical compound [O-]Cl=O QBWCMBCROVPCKQ-UHFFFAOYSA-M 0.000 description 1
- 229910001919 chlorite Inorganic materials 0.000 description 1
- 229910052619 chlorite group Inorganic materials 0.000 description 1
- 229960001701 chloroform Drugs 0.000 description 1
- BJIOGJUNALELMI-ARJAWSKDSA-N cis-isoeugenol Chemical compound COC1=CC(\C=C/C)=CC=C1O BJIOGJUNALELMI-ARJAWSKDSA-N 0.000 description 1
- 150000001924 cycloalkanes Chemical class 0.000 description 1
- 150000004816 dichlorobenzenes Chemical class 0.000 description 1
- DHCWLIOIJZJFJE-UHFFFAOYSA-L dichlororuthenium Chemical compound Cl[Ru]Cl DHCWLIOIJZJFJE-UHFFFAOYSA-L 0.000 description 1
- XOLNQIIEFUNTQC-UHFFFAOYSA-H dipotassium;hexachlororuthenium(2-) Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[K+].[K+].[Ru+4] XOLNQIIEFUNTQC-UHFFFAOYSA-H 0.000 description 1
- DXMRKRXRMGYFDG-UHFFFAOYSA-N dipotassium;hydrogen borate Chemical compound [K+].[K+].OB([O-])[O-] DXMRKRXRMGYFDG-UHFFFAOYSA-N 0.000 description 1
- FVJFRFUSHCIRKP-UHFFFAOYSA-N disodium;hydrogen borate Chemical compound [Na+].[Na+].OB([O-])[O-] FVJFRFUSHCIRKP-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- YIWFBNMYFYINAD-UHFFFAOYSA-N ethenylcyclopropane Chemical class C=CC1CC1 YIWFBNMYFYINAD-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000011552 falling film Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- YYWGABLTRMRUIT-HWWQOWPSSA-N huperzine b Chemical compound N1CCC[C@@H]2[C@H]3C=C(C)C[C@]21C(C=CC(=O)N1)=C1C3 YYWGABLTRMRUIT-HWWQOWPSSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002432 hydroperoxides Chemical class 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 150000004966 inorganic peroxy acids Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052743 krypton Inorganic materials 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- LWXVCCOAQYNXNX-UHFFFAOYSA-N lithium hypochlorite Chemical compound [Li+].Cl[O-] LWXVCCOAQYNXNX-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- YZQBYALVHAANGI-UHFFFAOYSA-N magnesium;dihypochlorite Chemical compound [Mg+2].Cl[O-].Cl[O-] YZQBYALVHAANGI-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- CCRCUPLGCSFEDV-BQYQJAHWSA-N methyl trans-cinnamate Chemical class COC(=O)\C=C\C1=CC=CC=C1 CCRCUPLGCSFEDV-BQYQJAHWSA-N 0.000 description 1
- 238000007040 multi-step synthesis reaction Methods 0.000 description 1
- ALHUZKCOMYUFRB-UHFFFAOYSA-N muskone Natural products CC1CCCCCCCCCCCCC(=O)C1 ALHUZKCOMYUFRB-UHFFFAOYSA-N 0.000 description 1
- 229910052754 neon Inorganic materials 0.000 description 1
- 229910052756 noble gas Inorganic materials 0.000 description 1
- 150000002835 noble gases Chemical class 0.000 description 1
- 150000004967 organic peroxy acids Chemical class 0.000 description 1
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- SATVIFGJTRRDQU-UHFFFAOYSA-N potassium hypochlorite Chemical compound [K+].Cl[O-] SATVIFGJTRRDQU-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- OJLCQGGSMYKWEK-UHFFFAOYSA-K ruthenium(3+);triacetate Chemical compound [Ru+3].CC([O-])=O.CC([O-])=O.CC([O-])=O OJLCQGGSMYKWEK-UHFFFAOYSA-K 0.000 description 1
- QQQRUHDQRQDWHW-UHFFFAOYSA-J ruthenium(4+);disulfate Chemical compound [Ru+4].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O QQQRUHDQRQDWHW-UHFFFAOYSA-J 0.000 description 1
- RQPOMTUDFBZCHG-UHFFFAOYSA-N ruthenium;trihydrate Chemical compound O.O.O.[Ru] RQPOMTUDFBZCHG-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- BJIOGJUNALELMI-UHFFFAOYSA-N trans-isoeugenol Natural products COC1=CC(C=CC)=CC=C1O BJIOGJUNALELMI-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/30—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with halogen containing compounds, e.g. hypohalogenation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/385—Saturated compounds containing a keto group being part of a ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/18—Systems containing only non-condensed rings with a ring being at least seven-membered
Definitions
- the present invention relates to a process for preparing a macrocyclic diketone compound of the formula (I), which comprises the oxidation of a bicycloolefine compound of the formula (II) with an oxidizing agent, where in formulae (I) and (II)
- Macrocyclic diketons of the formula (I), in particular cyclopentadecane-1,5-dione or 3-methylcyclopentadecane-1,5-dione, which correspond to formula (I), where A is CH 2 or CH-CH 3 and B is (CH 2 )8, are interesting fragrances and may also serve as precursors for other macrocyclic musk odorants, such as muscone.
- CH 519454 describes the preparation of cyclopentadecane-1,5-dione by ozonolysis of bicyclo[10.3.0]pentadecen[1(12)] or photooxidation of bicyclo[10.3.0]pentadecen[1(12)] with singlet oxygen, followed by acidic rearrangement of the resulting hydroperoxides.
- CH 519454 also describes the reaction of bicyclo[10.3.0]pentadecen[1(12)] with potassium permanganate. Ozonolysis and photooxidation are difficult to handle on large scale, while the use of potassium permanganate is comparatively expensive and requires a difficult and laborious work-up procedure.
- CH 513791 describes a process for the preparation of cyclopentadecane-1,5-dione and 3-methylcyclopentadecane-1,5-dione, comprising the oxidation of bicyclo[10.3.0]pentadecen[1(12)] or 14-methylbicyclo[10.3.0]pentadecen[1(12)] with a sub-stoichiometric amount of 55 % aqueous H 2 0 2 in concentrated formic acid followed by reacting the intermediates with potassium hydroxide to yield bicyclo[10.3.0]pentadecan-1,12-diol or 14-methylbicyclo[10.3.0]pentadecan-1,12-diol, which is then cleaved by treatment with Pb 3 O 4 in glacial acetic acid. The process is tedious and includes the use of toxic chemicals.
- CN 102786398A describes the multi-step synthesis of 3-methylcyclopentadecane-1,5-dione starting from cyclododecanone, wherein the last step of the synthesis comprises the oxidation of 14-methylbicyclo[10.3.0]pentadecen[1(12)] with stoichiometric amounts of sodium periodate in the presence of the phase transfer catalyst tetrabutylammonium bromide to yield 3-methylcyclopentadecane-1,5-dione.
- Sodium periodate which has to be applied in a more than four fold excess, is expensive and not easy to handle on industrial scales due to the high technical safety-requirements. Furthermore, the sodium periodate-waste has to be disposed. Due to these requirements and economical aspects, this process is inapplicable to industrial scale production.
- Ayres et al., Tetrahedron, Vol. 42, No. 15, pp. 4259 - 4265 describe the selective oxidation of phenolic alkenes with ruthenium tetroxide. Specifically, the oxidation of trifluoroacetylated isoeugenol, trifluoroacetylated 4,4'-dihydroxy- ⁇ , ⁇ -dimethylstilbene and a rearrangement product of trifluoroacetylated norpregnenol with stoichiometric amounts of ruthenium tetroxide using carbon tetrachloride as solvent is described.
- DE 3610718 describes a process for the production of glutaric acid, comprising the oxidation of cyclopentene using catalytic amounts of a ruthenium compound as oxidizing agent and stoichiometric amounts of a co-oxidizing agent, such as sodium hypochlorite.
- the oxidizing agent as well as the co-oxidizing agent is added in the form of an aqueous alkaline solution.
- the reaction is performed in a biphasic solvent system consisting of water and a chlorinated organic solvent.
- the process should be easy to handle and should allow the production of the compounds of formula (I) in good yields on industrial scales. Moreover, the use of toxic or expensive reagents should be avoided.
- the compounds of formula (II), in particular the compounds of formula (IIa), can be efficiently converted into the diketone compounds of formula (I), in particular into compounds of formula (Ia), if the oxidation of (II) or (IIa), respectively, is performed by using an oxidizing agent which comprises a catalytic amount of a ruthenium compound and a co-oxidizing agent selected from oxyanions of chlorine.
- the present invention relates to a process for producing a diketone compound of formula (I) as described herein, which comprises the oxidation of the bicyloolefine compound of formula (II) with an oxidizing agent, where the oxidizing agent comprises a catalytic amount of a ruthenium compound and a co-oxidizing agent selected from oxyanions of chlorine.
- the process according to the invention has several advantages over the prior art.
- the oxidation of the compounds of formula (II), in particular of the compounds of formula (IIa), by using a catalytic amount of a ruthenium compound as the oxidizing agent together with a co-oxidizing agent selected from oxyanions of chlorine by the process as described herein, directly results in the formation of the compounds of formulae (I) or (Ia), respectively, with good yields and selectivity.
- a catalytic amount of a ruthenium compound as the oxidizing agent together with a co-oxidizing agent selected from oxyanions of chlorine
- the present process can be easily performed on large scale, as the ruthenium compound as well as the co-oxidant are selected from nonhazardous compounds, and are, thus, much easier to handle than ozone, singlet oxygen, Pb 3 O 4 or sodium periodate. Moreover, the use of expensive oxidants can be avoided and the ruthenium compound can be recycled for further use. As the reaction proceeds smoothly and with high selectivity, tedious work-up and large waste streams can be avoided.
- ruthenates relates to any ruthenium salt containing the oxyanion RuO 4 2- .
- perruthenates relates to any ruthenium salt containing the oxyanion RuO 4 - .
- the total amount of ruthenium compound in the reaction mixture is typically in the range of from 0.001 to 0.2 mol, preferably in the range of from 0.005 to 0.15 mol, in particular in the range of from 0.01 to 0.1 mol, per 1 mol of compound of formula (II).
- any ruthenium compound in the form of an inorganic ruthenium salt or an organic complex salt can be used as oxidizing agent in the process of the present invention.
- Suitable ruthenium compounds are for example
- the above ruthenium compounds may be anhydrous or hydrated.
- the ruthenium compound may be used alone or in combination of two or more.
- the ruthenium compound used in the process of the invention is selected from ruthenium oxides, ruthenates, perruthenates, ruthenium halides, ruthenium nitrates and mixtures thereof.
- Preferred ruthenium oxides are for example ruthenium tetroxide or ruthenium dioxide.
- Preferred ruthenates are for example magnesium ruthenate, calcium ruthenate or sodium ruthenate.
- a preferred perruthenate is for example sodium perruthenate.
- Preferred ruthenium halides are for example ruthenium(III) chloride, ruthenium(IV) chloride or ruthenium(III) bromide.
- a preferred ruthenium nitrate is for example ruthenium(III) nitrate.
- the ruthenium compound used in the process of the present invention is selected from ruthenium tetroxide, sodium ruthenate, sodium perruthenate, ruthenium dioxide, ruthenium trichloride or mixtures thereof.
- the ruthenium compound used in the process of the invention is ruthenium trichloride.
- the total amount of co-oxidizing agent used in the oxidation is typically in the range of from 2 to 10 mol, in particular in the range of from 3 to 8 mol, per 1 mol of compound of formula (II), whereby the molar amount of the oxidizing-agent specified above is calculated as oxygen equivalents.
- oxygen equivalent relates to the number of oxygen atoms that can be released by a given oxidant.
- inorganic or organic peroxy acids as well as H 2 O 2 can release one oxygen atom.
- Hypochlorite (ClO - ) can also release one oxygen atom, while chlorite (ClO 2 - ) can typically release two oxygen atoms.
- the co-oxidizing agent is selected from oxyanions of chlorine.
- any oxyanion of chlorine that is capable of oxidizing a ruthenium compound having a low oxidation number to generate a ruthenium compound that is able to oxidize olefins can be used as co-oxidizing agent in the process of the present invention.
- Suitable oxyanions of chlorine are by way of example hypochlorites, chlorites, chlorates or perchlorates.
- hypochlorites relate to any salt containing the oxyanion ClO - (hypochlorite), ClO 2 - (chlorite), ClO 3 - (chlorate) or ClO 4 - (perchlorate), respectively, e.g. the alkali or earth alkali metal salts thereof.
- the co-oxidizing agent is selected from hypochlorites, e.g. lithium hypochlorite, sodium hypochlorite, potassium hypochlorite, magnesium hypochlorite, calcium hypochlorite, or barium hypochlorite; in particular it is sodium hypochlorite.
- hypochlorites e.g. lithium hypochlorite, sodium hypochlorite, potassium hypochlorite, magnesium hypochlorite, calcium hypochlorite, or barium hypochlorite; in particular it is sodium hypochlorite.
- the ruthenium compound preferably the total amount of the ruthenium compound, is added to the compound of formulae (II) or (IIa) at the start of the reaction.
- the co-oxidizing agent can be added at the start of the oxidation reaction or over the course of the oxidation reaction.
- the expression "course of the reaction” relates to the time interval between the start of the oxidation reaction, i.e. when the ruthenium compound and the compound of formula (II) or (IIa) are brought together and the reaction parameters are such that the oxidation reaction can take place, and the end of the reaction, i.e. when the compound of formula (II) or (IIa) is consumed and/or no further compound (I) or (Ia) is formed.
- the co-oxidizing agent is added over the course of the reaction. Thereby it is achieved that a steady amount of co-oxidizing agent is present in the reaction mixture. Adding the co-oxidizing agent over the course of the reaction is beneficial with regard to clean and rapid conversion.
- the co-oxidizing agent can be added to the mixture of the compound of formulae (II) or (IIa) in one or more portions or continuously with constant or changing addition rates.
- the co-oxidizing agent is added in several portions, e.g. in 3 to 20 portions, or continuously, preferably with constant addition rates, to the mixture of the compound of formulae (II) or (IIa).
- the co-oxidizing agent is added in several portions, e.g. in defined amounts in regular time intervals, for example every 10 to 90 minutes, e.g. every 30 or 60 minutes, or continuously with constant addition rates to the mixture of the compound of formulae (II) or (IIa) over the whole course of the oxidation reaction.
- reaction time is in the range of from 1 to 16 hours, often in the range of from 1.5 to 12 hours.
- the co-oxidizing agent is added to the reaction mixture in the form of an alkaline aqueous solution, having a pH of at least pH 10, preferably of at least pH 12, for example pH 13 or pH 14.
- the concentration of the co-oxidizing agent in the alkaline aqueous solution is in the range of from 1 to 50 % by weight, preferably in the range of from 3 to 30 % by weight, in particular in the range of from 5 to 20 % by weight.
- the alkaline aqueous solution is for example conveniently prepared by adding a strong mineral base, e.g. NaOH, KOH, or LiOH, in the form of a solid or an aqueous solution to an aqueous solution of the co-oxidizing agent.
- a strong mineral base e.g. NaOH, KOH, or LiOH
- the final concentration of the mineral base in the alkaline aqueous solution of the co-oxidizing agent is in the range of from 0,01 to 10 molar, preferably in the range of from 0,05 to 5 molar, in particular in the range of from 0,1 to 2 molar.
- the molar ratio of the co-oxidizing agent to the ruthenium compound, which are applied to the reaction mixture is in the range from 10 : 1 to 10000 : 1, preferably in the range of from 1 : 1 to 5000 : 1, in particular in the range of from 1 : 5 to 1000 : 1.
- the oxidation of the compound of formulae (II) or (IIa) to give the compound of formulae (I) or (Ia) is conducted in such a way, that the pH of the reaction mixture is maintained in the range of from 7 to 14, preferably in the range of from 7 to 12, particularly in the range of from 7.5 to 11, and especially in the range of from 8.0 to 10.9.
- the pH values given above relate to the pH of the aqueous phase of the reaction mixture, which results from the addition of the alkaline aqueous solution of the co-oxidizing agent to the reaction mixture comprising a water immiscible organic solvent, measured at 25 °C.
- the maintenance of the pH of the reaction mixture can be achieved by varying the pH of the alkaline aqueous solution of the co-oxidizing agent, e.g. by varying the concentration of the added mineral base, by adapting the addition rate of the alkaline aqueous solution of the co-oxidizing agent to the reaction mixture and/or by adding an aqueous buffer solution, comprising at least one buffering agent having a pKa-value in the range of from 8 to 12, to the reaction mixture.
- the maintenance of the pH of the reaction mixture is either achieved by varying the pH of the alkaline aqueous solution of the co-oxidizing agent, e.g. by varying the concentration of the added mineral base, by adapting the addition rate of the alkaline aqueous solution of the co-oxidizing agent to the reaction mixture or by adding an aqueous buffer solution, comprising at least one buffering agent having a pKa-value in the range of from 8 to 12, to the reaction mixture.
- any compound having a pKa-value in the range of from 8 to 12 is suitable as buffering agent.
- Suitable buffering agents having a pKa-value in the range of from 8 to 12 are for example selected from sodium hydrogen carbonate, potassium hydrogen carbonate, lithium carbonate, sodium carbonate, potassium carbonate, ammonium chloride, boric acid, sodium hydrogen borate, potassium hydrogen borate and mixtures thereof.
- the buffering agent is selected from sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, ammonium chloride ammonium, and mixtures thereof.
- the buffering agent is selected from a mixture of sodium hydrogen carbonate with sodium carbonate or potassium hydrogen carbonate with potassium carbonate.
- the concentration of the at least one buffering agent in the aqueous buffer solution is in the range of from 0.01 to 5 molar, preferably in the range of from 0.1 to 2 molar.
- the amount of the aqueous buffer solution that is added to the reaction mixture highly depends on the total concentration of the buffering agent in the aqueous buffer solution.
- the amount of the aqueous buffer solution that is added to the reaction mixture is chosen such that the pH of the reaction mixture does not vary more than 4 pH units, preferably not more than 3 pH units, in particular not more than 2 pH units, over the whole course of the reaction.
- the pH of the buffering solution is in the range of from 7 to 11, preferably in the range of from 8 to 10.
- the aqueous buffer solution can be added to the mixture of the compound of formulae (II) or (IIa) in one or more portions or continuously with constant or changing addition rates.
- the co-oxidizing agent is added in one portion to the mixture of the compound of formulae (II) or (IIa) at the start of the oxidation reaction.
- reaction can be principally performed in accordance with standard procedures of organic chemistry.
- the temperature which is required to achieve the oxidation of the compound of formulae (II) or (IIa) to the compound of formulae (I) or (Ia) may vary. Frequently, the oxidation of the compound of formulae (II) or (IIa) to the compound of formulae (I) or (Ia), respectively, is performed at a temperature in the range of from -20 to 100°C, in particular from 0 to 80°C and especially from 10 to 40°C.
- reaction pressure is of minor importance.
- the reaction is performed in a non-pressured vessel having pressurized balance with the ambient air.
- the oxidation reaction can take place in the absence of or in the presence of an inert gas.
- inert gas generally means a gas which under the prevailing reaction conditions does not enter into any reactions with the starting materials, reagents, or solvents participating in the reaction, nor with the resultant products.
- inert gases are N 2 , CO 2 and noble gases like He, Ne, Ar, Kr and Xe. If the oxidation reaction is performed in the presence of an inert gas, the inert gas is preferably selected from N 2 or Ar.
- the oxidation of the compounds of formulae (II) or (IIa) to give the compounds of formulae (I) or (Ia) can be carried out in bulk, i.e. in the absence of any added solvent or in the presence of one or more organic solvents.
- the oxidation of the compounds of formulae (II) or (IIa) to give the compounds of formulae (I) or (Ia) is performed in the presence of an organic solvent or an organic solvent mixture.
- the organic solvent is inert under the reaction conditions.
- Preferred inert organic solvents are, by way of example, aliphatic or alicyclic hydrocarbons, in particular alkanes and cycloalkanes having 5 to 12 carbon atoms, halogenated aliphatic hydrocarbons, and aromatic and substituted aromatic hydrocarbons, aliphatic or alicyclic ethers and alkyl esters.
- inert solvents examples include aliphatic hydrocarbons, such as pentane, hexane, heptane, ligroin, petrol ether, cyclohexane, halogenated hydrocarbons, such as dichloromethane, trichloromethane, tetrachloromethane or dichloroethane, aromatics, such as benzene, toluene, xylenes, chlorobenzene, dichlorobenzenes, aliphatic or alicyclic ethers such as methyl-tert.-butylether, dibutyl ether, tetrahydrofurane, 1,4-dioxane, 1,2-dimethoxyethane, alkyl esters, such as ethyl acetate or propyl acetate, and mixtures thereof.
- aliphatic hydrocarbons such as pentane, hexane, heptane, ligroin
- the oxidation of the compounds of formulae (II) or (IIa) to the compounds of formulae (I) or (Ia) is performed in the presence of an organic solvent or an organic solvent mixture selected from water immiscible, non-halogenated organic solvents.
- inert organic solvents examples include aliphatic hydrocarbons, such as hexane, heptane, petrol ether or cyclohexane; aromatics, such as benzene, toluene or xylenes; ethers, such as methyl-tert.-butylether, dibutyl ether, tetrahydrofurane, 1,4-dioxane or 1,2-dimethoxyethane; alkyl esters, such as ethyl acetate or propyl acetate; and mixtures thereof. Especially preferred are methyl-tert.-butylether and ethyl acetate.
- the process of the invention can be performed either continuously or batchwise.
- the batchwise oxidation can be conducted in a reaction apparatus conventionally used for this purpose, e.g. a stirred reactor, which is optionally equipped with metering devices.
- the process according to the present invention may also be carried out continuously, e.g. in a tube reactor or in a cascade of at least two stirred reactors, which may be back-mixed or not.
- the reaction mixture can be subjected to conventional work-up including e.g. extractive aqueous work-up, removal of volatiles and the like.
- the ruthenium compound is recovered from the reaction mixture after completion of the oxidation of the compound of formula (II) or (IIa), respectively, for further use or reuse.
- the recycling of the ruthenium compound can for example be achieved by simple filtration of the organic phase, followed by one or several washing steps with water and/or the organic solvent. After the washing steps, the ruthenium compound may be dried for one to several hours, e.g. 2 or 3 hours, at elevated temperature, for example at a temperature of 40, 50 or 60°C. The thus obtained ruthenium compound can directly be used for further oxidation reactions.
- the ruthenium compound can also be reused directly after filtration without any washing and/or drying steps.
- the reaction mixture typically consist of two phases.
- the work-up procedure can for example conveniently be performed as follows: After completion of the reaction, the two phases are separated and the residual water phase is washed several times with the organic solvent, whereupon removal of the ruthenium compound by filtration and evaporation of the organic solvent, the compounds of formulae (I) or (Ia), respectively, are obtained as an crude product.
- distillation devices for the purification of the compounds of formulae (I) or (Ia), respectively, include, for example, distillation columns, such as tray columns optionally equipped with bubble cap trays, sieve plates, sieve trays, packages or filler materials, or spinning band columns, such as thin film evaporators, falling film evaporators, forced circulation evaporators, Sambay evaporators, etc. and combinations thereof.
- the starting compounds of the formulae (II) or (IIa) are known e.g. from DE 2916418 ; they are commercially available or they can be prepared by analogy to the methods described in DE 2916418 .
- GC-system Agilent 5890 Series II; GC-Column: 5CB-WAX-52CB (50 m (Length), 0.32 mm (ID), 1.2 ⁇ m (Film)); Temperature program: 40°C for 6 minutes, 40°C to until 250°C in 8°C/min.
- reaction mixture was allowed to cool down to room temperature and the organic phase was separated from the water phase.
- the water phase was washed with 1,2-dichloromethane.
- the ruthenium compound (catalyst) was separated from the organic phase by filtration and washed with 1,2-dichloromethane and water.
- the combined organic phases were dried over sodium sulfate and the solvent was removed under reduced pressure.
- An analysis of the reaction residual revealed 100% conversion of the monoene (IIa) and the formation of the wanted diketone of formula (Ia) of 95% (GC weight percent).
- Example 2 Oxidation of IIa in ethyl acetate and in the presence of a buffer solution
- reaction mixture was allowed to cool down to room temperature and the organic phase was separated from the water phase.
- the water phase was washed with ethyl acetate.
- the ruthenium compound (catalyst) was separated from the organic phase by filtration and washed with ethyl acetate and water.
- the combined organic phases were dried over sodium sulfate and the solvent was removed under reduced pressure.
- An analysis of the reaction residual revealed 100% conversion of the monoene (IIa) and the formation of the wanted diketone of formula (Ia) of 83.5% (GC weight percent).
- reaction mixture was allowed to cool down to room temperature and the organic phase was separated from the water phase.
- the water phase was washed with ethyl acetate.
- the ruthenium compound (catalyst) was separated from the organic phase by filtration and washed with ethyl acetate and water.
- the combined organic phases were dried over sodium sulfate and the solvent was removed under reduced pressure.
- An analysis of the reaction residual revealed 100 % conversion of the monoene (IIa) and the formation of the wanted diketone of formula (Ia) of 75.8% (GC weight percent).
- Example 4 Oxidation of IIa in methyl tert.-butyl ether (MTBE) and in the presence of a buffer solution
- reaction mixture was allowed to cool down to room temperature and the organic phase was separated from the water phase.
- the water phase was washed with MTBE.
- the ruthenium compound (catalyst) was separated from the organic phase by filtration and washed with MTBE and water.
- the combined organic phases were dried over sodium sulfate and the solvent was removed under reduced pressure.
- An analysis of the reaction residual revealed 100% conversion of the monoene (IIa) and the formation of the wanted diketone of formula (Ia) of 66.3% (GC weight percent).
- Example 5 Oxidation of Ila in methyl tert.-butyl ether (MTBE) without the addition of a buffer solution
- reaction mixture was allowed to cool down to room temperature and the organic phase was separated from the water phase.
- the water phase was washed with MTBE.
- the ruthenium compound (catalyst) was separated from the organic phase by filtration and washed with MTBE and water.
- the combined organic phases were dried over sodium sulfate and the solvent was removed under reduced pressure.
- An analysis of the reaction residual revealed 100% conversion of the monoene (IIa) and the formation of the wanted diketone of formula (Ia) of 93.6% (GC weight percent).
- the reaction mixture was allowed to cool down to room temperature and the organic phase was separated from the water phase.
- the water phase was washed with MTBE.
- the organic phase was first washed with 250 ml of a 20 weight-% solution of NaOH in water followed by 250 ml of water.
- the ruthenium compound (catalyst) was separated from the organic phase by filtration and washed with MTBE and water. After this washing step, the ruthenium compound (catalyst) was dried at 50°C for 2 hours and directly applied to the next oxidation reaction (vide example 7).
- Example 7 Large batch oxidation of IIa in methyl tert.-butyl ether (MTBE) using the recovered ruthenium compound (catalyst) of example 6
- the reaction mixture was allowed to cool down to room temperature and the organic phase was separated from the water phase.
- the water phase was washed with MTBE.
- the organic phase was first washed with 250 ml of a 20 weight-% solution of NaOH in water followed by 250 ml of water.
- the ruthenium compound (catalyst) was separated from the organic phase by filtration and washed with MTBE and water. After this washing step, the ruthenium compound (catalyst) was dried at 50°C for 2 hours.
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
-
- A
- is (CH2)n with n being an integer from 2 to 12, in particular 6 to 10, where two hydrogen atoms may be replaced by C1-C4-alkyl, in particular methyl, or two hydrogen atoms, which are bound to adjacent carbon atoms may be replaced by a fused 5- or 6-membered saturated carbocycle;
- B
- is (CH2)m with m being 1 or 2, where 1 or 2 hydrogen atoms may be replaced by C1-C4-alkyl, in particular methyl.
- Macrocyclic diketons of the formula (I), in particular cyclopentadecane-1,5-dione or 3-methylcyclopentadecane-1,5-dione, which correspond to formula (I), where A is CH2 or CH-CH3 and B is (CH2)8, are interesting fragrances and may also serve as precursors for other macrocyclic musk odorants, such as muscone.
- The preparation of macrocyclic diketones via oxidative cleavage of the double bond of bicycloolefine compounds is known in the art.
-
CH 519454 CH 519454 -
CH 513791 -
CN 102786398A describes the multi-step synthesis of 3-methylcyclopentadecane-1,5-dione starting from cyclododecanone, wherein the last step of the synthesis comprises the oxidation of 14-methylbicyclo[10.3.0]pentadecen[1(12)] with stoichiometric amounts of sodium periodate in the presence of the phase transfer catalyst tetrabutylammonium bromide to yield 3-methylcyclopentadecane-1,5-dione. Sodium periodate, which has to be applied in a more than four fold excess, is expensive and not easy to handle on industrial scales due to the high technical safety-requirements. Furthermore, the sodium periodate-waste has to be disposed. Due to these requirements and economical aspects, this process is inapplicable to industrial scale production. - The oxidation of substituted olefins with ruthenium compounds is generally known in the art.
- Lee et al., J. Org. Chem., 1976, Vol. 41 (22), pp. 3644 - 3644, for example, describe the oxidation of methyl cinnamate compounds with stoichiometric amounts of ruthenium tetroxide.
- Ayres et al., Tetrahedron, Vol. 42, No. 15, pp. 4259 - 4265, describe the selective oxidation of phenolic alkenes with ruthenium tetroxide. Specifically, the oxidation of trifluoroacetylated isoeugenol, trifluoroacetylated 4,4'-dihydroxy-α,β-dimethylstilbene and a rearrangement product of trifluoroacetylated norpregnenol with stoichiometric amounts of ruthenium tetroxide using carbon tetrachloride as solvent is described.
- Sonawane et al., Tetrahedron Letters, Vol. 33, No. 12, pp.1645 - 1646, describe a thermal transformation of spirocyclic vinylcyclopropanes to bicyclo [m.3.0] bridged alkenes. The use of an oxyanion of chlorine as co-oxidizing anion is not mentioned.
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DE 3610718 describes a process for the production of glutaric acid, comprising the oxidation of cyclopentene using catalytic amounts of a ruthenium compound as oxidizing agent and stoichiometric amounts of a co-oxidizing agent, such as sodium hypochlorite. The oxidizing agent as well as the co-oxidizing agent is added in the form of an aqueous alkaline solution. The reaction is performed in a biphasic solvent system consisting of water and a chlorinated organic solvent. - To date, all reported processes for the oxidation of 14-methylbicyclo[10.3.0]pentadecen[1(12)] or bicyclo[10.3.0]pentadecen[1(12)] have major disadvantages when they are applied to industrial scale production.
- Therefore, it is an object of the present invention to provide a process for efficiently producing the compound of formula (I), in particular cyclopentadecane-1,5-dione and 3-methylcyclopentadecane-1,5-dione. The process should be easy to handle and should allow the production of the compounds of formula (I) in good yields on industrial scales. Moreover, the use of toxic or expensive reagents should be avoided.
- It was surprisingly found that the compounds of formula (II), in particular the compounds of formula (IIa), can be efficiently converted into the diketone compounds of formula (I), in particular into compounds of formula (Ia), if the oxidation of (II) or (IIa), respectively, is performed by using an oxidizing agent which comprises a catalytic amount of a ruthenium compound and a co-oxidizing agent selected from oxyanions of chlorine.
- Therefore, the present invention relates to a process for producing a diketone compound of formula (I) as described herein, which comprises the oxidation of the bicyloolefine compound of formula (II) with an oxidizing agent, where the oxidizing agent comprises a catalytic amount of a ruthenium compound and a co-oxidizing agent selected from oxyanions of chlorine.
- The present invention relates in particular to a process for producing 3-methylcyclopentadecane-1,5-dione of formula (la, R = CH3) from 14-methylbicyclo[10.3.0]pentadecen[1(12)] of formula (IIa, R = CH3), by the process as described herein.
- The present invention also relates in particular to a process for producing cyclopentadecane-1,5-dione of formula (la, R = H) from bicyclo[10.3.0]pentadecen[1(12)] of formula (IIa, R = H), by the process as described herein.
- The process according to the invention has several advantages over the prior art. The oxidation of the compounds of formula (II), in particular of the compounds of formula (IIa), by using a catalytic amount of a ruthenium compound as the oxidizing agent together with a co-oxidizing agent selected from oxyanions of chlorine by the process as described herein, directly results in the formation of the compounds of formulae (I) or (Ia), respectively, with good yields and selectivity. In contrast to the processes described in the art, e.g. in
CH 513791 CH 519454 CN 102786398A , the present process can be easily performed on large scale, as the ruthenium compound as well as the co-oxidant are selected from nonhazardous compounds, and are, thus, much easier to handle than ozone, singlet oxygen, Pb3O4 or sodium periodate. Moreover, the use of expensive oxidants can be avoided and the ruthenium compound can be recycled for further use. As the reaction proceeds smoothly and with high selectivity, tedious work-up and large waste streams can be avoided. - For the purpose of the present invention, the expression "ruthenates" relates to any ruthenium salt containing the oxyanion RuO4 2-.
- For the purpose of the present invention, the expression "perruthenates" relates to any ruthenium salt containing the oxyanion RuO4 -.
- According to the process of the present invention, the total amount of ruthenium compound in the reaction mixture, calculated based on the number of ruthenium atoms, is typically in the range of from 0.001 to 0.2 mol, preferably in the range of from 0.005 to 0.15 mol, in particular in the range of from 0.01 to 0.1 mol, per 1 mol of compound of formula (II).
- Generally, any ruthenium compound in the form of an inorganic ruthenium salt or an organic complex salt can be used as oxidizing agent in the process of the present invention. Suitable ruthenium compounds are for example
- ruthenium oxides, such as ruthenium(IV)oxide or ruthenium(VIII)oxide;
- ruthenates, i.e. any ruthenium salt containing the oxyanion RuO4 2-, e.g. the alkali or earth alkali metal salts thereof, such as magnesium-, strontium-, calcium-, barium- or sodium ruthenate;
- perruthenates, i.e. any ruthenium salt containing the oxyanion RuO4 -, e.g. the alkali or earth alkali metal salts thereof, such as sodium- or potassium perruthenates;
- ruthenium halides, such as ruthenium(II) chloride, ruthenium(III) chloride, ruthenium(IV) chloride, ruthenium(III) bromide or ruthenium(III) iodide;
- ruthenium nitrates, such as ruthenium(III) nitrate;
- ruthenium(III) hydroxide;
- ruthenium(IV) sulfate;
- ruthenium carboxylates, such as ruthenium(III) acetate;
- ruthenium complexes, such as ammonium hexachlororuthenate(IV), potassium hexachlororuthenate(IV), ammonium pentachloroaquaruthenate(III), potassium pentachloroaquaruthenate(III), hexaammine ruthenium(III) chloride, hexaammine ruthenium(III) bromide, hexaammine ruthenium(III) iodide, nitrosylpentaammine ruthenium(III) chloride, ruthenium(IV) ethylenediaminetetraacetate or ruthenium(0) dodecacarbonyl.
- The above ruthenium compounds may be anhydrous or hydrated. The ruthenium compound may be used alone or in combination of two or more.
- Preferably, the ruthenium compound used in the process of the invention is selected from ruthenium oxides, ruthenates, perruthenates, ruthenium halides, ruthenium nitrates and mixtures thereof.
- Preferred ruthenium oxides are for example ruthenium tetroxide or ruthenium dioxide. Preferred ruthenates are for example magnesium ruthenate, calcium ruthenate or sodium ruthenate.
- A preferred perruthenate is for example sodium perruthenate.
- Preferred ruthenium halides are for example ruthenium(III) chloride, ruthenium(IV) chloride or ruthenium(III) bromide.
- A preferred ruthenium nitrate is for example ruthenium(III) nitrate.
- More preferably, the ruthenium compound used in the process of the present invention is selected from ruthenium tetroxide, sodium ruthenate, sodium perruthenate, ruthenium dioxide, ruthenium trichloride or mixtures thereof.
- In particular, the ruthenium compound used in the process of the invention is ruthenium trichloride.
- According to the process of the invention, the total amount of co-oxidizing agent used in the oxidation is typically in the range of from 2 to 10 mol, in particular in the range of from 3 to 8 mol, per 1 mol of compound of formula (II), whereby the molar amount of the oxidizing-agent specified above is calculated as oxygen equivalents.
- For the purposes of the present invention, the term "oxygen equivalent" relates to the number of oxygen atoms that can be released by a given oxidant. For example, inorganic or organic peroxy acids as well as H2O2 can release one oxygen atom. Hypochlorite (ClO-) can also release one oxygen atom, while chlorite (ClO2 -) can typically release two oxygen atoms.
- According to the invention, the co-oxidizing agent is selected from oxyanions of chlorine. In principal, any oxyanion of chlorine that is capable of oxidizing a ruthenium compound having a low oxidation number to generate a ruthenium compound that is able to oxidize olefins can be used as co-oxidizing agent in the process of the present invention.
- Suitable oxyanions of chlorine are by way of example hypochlorites, chlorites, chlorates or perchlorates.
- For the purpose of the present invention, the expressions "hypochlorites", "chlorites", "chlorates" or "perchlorates" relate to any salt containing the oxyanion ClO- (hypochlorite), ClO2 - (chlorite), ClO3 - (chlorate) or ClO4 - (perchlorate), respectively, e.g. the alkali or earth alkali metal salts thereof.
- In particular, the co-oxidizing agent is selected from hypochlorites, e.g. lithium hypochlorite, sodium hypochlorite, potassium hypochlorite, magnesium hypochlorite, calcium hypochlorite, or barium hypochlorite; in particular it is sodium hypochlorite.
- Generally, at least a part of the ruthenium compound, preferably the total amount of the ruthenium compound, is added to the compound of formulae (II) or (IIa) at the start of the reaction.
- The co-oxidizing agent can be added at the start of the oxidation reaction or over the course of the oxidation reaction. The expression "course of the reaction" relates to the time interval between the start of the oxidation reaction, i.e. when the ruthenium compound and the compound of formula (II) or (IIa) are brought together and the reaction parameters are such that the oxidation reaction can take place, and the end of the reaction, i.e. when the compound of formula (II) or (IIa) is consumed and/or no further compound (I) or (Ia) is formed. It is preferred that the co-oxidizing agent is added over the course of the reaction. Thereby it is achieved that a steady amount of co-oxidizing agent is present in the reaction mixture. Adding the co-oxidizing agent over the course of the reaction is beneficial with regard to clean and rapid conversion.
- The co-oxidizing agent can be added to the mixture of the compound of formulae (II) or (IIa) in one or more portions or continuously with constant or changing addition rates. Preferably, the co-oxidizing agent is added in several portions, e.g. in 3 to 20 portions, or continuously, preferably with constant addition rates, to the mixture of the compound of formulae (II) or (IIa).
- It has been found beneficial, if the co-oxidizing agent is added in several portions, e.g. in defined amounts in regular time intervals, for example every 10 to 90 minutes, e.g. every 30 or 60 minutes, or continuously with constant addition rates to the mixture of the compound of formulae (II) or (IIa) over the whole course of the oxidation reaction.
- Typically, the reaction time is in the range of from 1 to 16 hours, often in the range of from 1.5 to 12 hours.
- In a preferred embodiment of the present invention, the co-oxidizing agent is added to the reaction mixture in the form of an alkaline aqueous solution, having a pH of at least pH 10, preferably of at least pH 12, for example pH 13 or pH 14.
- In this preferred embodiment, the concentration of the co-oxidizing agent in the alkaline aqueous solution is in the range of from 1 to 50 % by weight, preferably in the range of from 3 to 30 % by weight, in particular in the range of from 5 to 20 % by weight.
- The alkaline aqueous solution is for example conveniently prepared by adding a strong mineral base, e.g. NaOH, KOH, or LiOH, in the form of a solid or an aqueous solution to an aqueous solution of the co-oxidizing agent. Generally the final concentration of the mineral base in the alkaline aqueous solution of the co-oxidizing agent is in the range of from 0,01 to 10 molar, preferably in the range of from 0,05 to 5 molar, in particular in the range of from 0,1 to 2 molar.
- Generally, the molar ratio of the co-oxidizing agent to the ruthenium compound, which are applied to the reaction mixture, is in the range from 10 : 1 to 10000 : 1, preferably in the range of from 1 : 1 to 5000 : 1, in particular in the range of from 1 : 5 to 1000 : 1.
- In a particular embodiment of the present invention, the oxidation of the compound of formulae (II) or (IIa) to give the compound of formulae (I) or (Ia) is conducted in such a way, that the pH of the reaction mixture is maintained in the range of from 7 to 14, preferably in the range of from 7 to 12, particularly in the range of from 7.5 to 11, and especially in the range of from 8.0 to 10.9.
- The pH values given above relate to the pH of the aqueous phase of the reaction mixture, which results from the addition of the alkaline aqueous solution of the co-oxidizing agent to the reaction mixture comprising a water immiscible organic solvent, measured at 25 °C.
- The maintenance of the pH of the reaction mixture can be achieved by varying the pH of the alkaline aqueous solution of the co-oxidizing agent, e.g. by varying the concentration of the added mineral base, by adapting the addition rate of the alkaline aqueous solution of the co-oxidizing agent to the reaction mixture and/or by adding an aqueous buffer solution, comprising at least one buffering agent having a pKa-value in the range of from 8 to 12, to the reaction mixture.
- It is preferred that the maintenance of the pH of the reaction mixture is either achieved by varying the pH of the alkaline aqueous solution of the co-oxidizing agent, e.g. by varying the concentration of the added mineral base, by adapting the addition rate of the alkaline aqueous solution of the co-oxidizing agent to the reaction mixture or by adding an aqueous buffer solution, comprising at least one buffering agent having a pKa-value in the range of from 8 to 12, to the reaction mixture.
- In principal, any compound having a pKa-value in the range of from 8 to 12 is suitable as buffering agent. Suitable buffering agents having a pKa-value in the range of from 8 to 12, are for example selected from sodium hydrogen carbonate, potassium hydrogen carbonate, lithium carbonate, sodium carbonate, potassium carbonate, ammonium chloride, boric acid, sodium hydrogen borate, potassium hydrogen borate and mixtures thereof. Preferably, the buffering agent is selected from sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, ammonium chloride ammonium, and mixtures thereof. In particular, the buffering agent is selected from a mixture of sodium hydrogen carbonate with sodium carbonate or potassium hydrogen carbonate with potassium carbonate.
- Generally, the concentration of the at least one buffering agent in the aqueous buffer solution is in the range of from 0.01 to 5 molar, preferably in the range of from 0.1 to 2 molar.
- Typically, the amount of the aqueous buffer solution that is added to the reaction mixture highly depends on the total concentration of the buffering agent in the aqueous buffer solution. Preferably, the amount of the aqueous buffer solution that is added to the reaction mixture is chosen such that the pH of the reaction mixture does not vary more than 4 pH units, preferably not more than 3 pH units, in particular not more than 2 pH units, over the whole course of the reaction.
- Generally, the pH of the buffering solution is in the range of from 7 to 11, preferably in the range of from 8 to 10.
- The aqueous buffer solution can be added to the mixture of the compound of formulae (II) or (IIa) in one or more portions or continuously with constant or changing addition rates. Preferably, the co-oxidizing agent is added in one portion to the mixture of the compound of formulae (II) or (IIa) at the start of the oxidation reaction.
- The reaction can be principally performed in accordance with standard procedures of organic chemistry.
- The temperature which is required to achieve the oxidation of the compound of formulae (II) or (IIa) to the compound of formulae (I) or (Ia) may vary. Frequently, the oxidation of the compound of formulae (II) or (IIa) to the compound of formulae (I) or (Ia), respectively, is performed at a temperature in the range of from -20 to 100°C, in particular from 0 to 80°C and especially from 10 to 40°C.
- The reaction pressure is of minor importance. In particular, the reaction is performed in a non-pressured vessel having pressurized balance with the ambient air.
- The oxidation reaction can take place in the absence of or in the presence of an inert gas. The expression inert gas generally means a gas which under the prevailing reaction conditions does not enter into any reactions with the starting materials, reagents, or solvents participating in the reaction, nor with the resultant products.
- Examples of inert gases are N2, CO2 and noble gases like He, Ne, Ar, Kr and Xe. If the oxidation reaction is performed in the presence of an inert gas, the inert gas is preferably selected from N2 or Ar.
- The oxidation of the compounds of formulae (II) or (IIa) to give the compounds of formulae (I) or (Ia) can be carried out in bulk, i.e. in the absence of any added solvent or in the presence of one or more organic solvents.
- It is preferred that the oxidation of the compounds of formulae (II) or (IIa) to give the compounds of formulae (I) or (Ia) is performed in the presence of an organic solvent or an organic solvent mixture.
- If the oxidation reaction is carried out in the presence of an organic solvent, it is preferred that the organic solvent is inert under the reaction conditions. Preferred inert organic solvents are, by way of example, aliphatic or alicyclic hydrocarbons, in particular alkanes and cycloalkanes having 5 to 12 carbon atoms, halogenated aliphatic hydrocarbons, and aromatic and substituted aromatic hydrocarbons, aliphatic or alicyclic ethers and alkyl esters. Examples of inert solvents are aliphatic hydrocarbons, such as pentane, hexane, heptane, ligroin, petrol ether, cyclohexane, halogenated hydrocarbons, such as dichloromethane, trichloromethane, tetrachloromethane or dichloroethane, aromatics, such as benzene, toluene, xylenes, chlorobenzene, dichlorobenzenes, aliphatic or alicyclic ethers such as methyl-tert.-butylether, dibutyl ether, tetrahydrofurane, 1,4-dioxane, 1,2-dimethoxyethane, alkyl esters, such as ethyl acetate or propyl acetate, and mixtures thereof.
- In a particularly preferred embodiment of the present invention, the oxidation of the compounds of formulae (II) or (IIa) to the compounds of formulae (I) or (Ia) is performed in the presence of an organic solvent or an organic solvent mixture selected from water immiscible, non-halogenated organic solvents.
- Examples of particularly preferred inert organic solvents are aliphatic hydrocarbons, such as hexane, heptane, petrol ether or cyclohexane; aromatics, such as benzene, toluene or xylenes; ethers, such as methyl-tert.-butylether, dibutyl ether, tetrahydrofurane, 1,4-dioxane or 1,2-dimethoxyethane; alkyl esters, such as ethyl acetate or propyl acetate; and mixtures thereof. Especially preferred are methyl-tert.-butylether and ethyl acetate.
- The process of the invention can be performed either continuously or batchwise. The batchwise oxidation can be conducted in a reaction apparatus conventionally used for this purpose, e.g. a stirred reactor, which is optionally equipped with metering devices. The process according to the present invention may also be carried out continuously, e.g. in a tube reactor or in a cascade of at least two stirred reactors, which may be back-mixed or not.
- The reaction mixture can be subjected to conventional work-up including e.g. extractive aqueous work-up, removal of volatiles and the like.
- In a preferred embodiment of the present invention, the ruthenium compound is recovered from the reaction mixture after completion of the oxidation of the compound of formula (II) or (IIa), respectively, for further use or reuse.
- The recycling of the ruthenium compound can for example be achieved by simple filtration of the organic phase, followed by one or several washing steps with water and/or the organic solvent. After the washing steps, the ruthenium compound may be dried for one to several hours, e.g. 2 or 3 hours, at elevated temperature, for example at a temperature of 40, 50 or 60°C. The thus obtained ruthenium compound can directly be used for further oxidation reactions.
- Alternatively, the ruthenium compound can also be reused directly after filtration without any washing and/or drying steps.
- If a water immiscible organic solvent is used for the oxidation reaction and an alkaline aqueous solution of the co-oxidizing agent and/or an aqueous buffer solution are added to the reaction mixture, the reaction mixture typically consist of two phases. In this case, the work-up procedure can for example conveniently be performed as follows: After completion of the reaction, the two phases are separated and the residual water phase is washed several times with the organic solvent, whereupon removal of the ruthenium compound by filtration and evaporation of the organic solvent, the compounds of formulae (I) or (Ia), respectively, are obtained as an crude product.
- The obtained crude product may be subjected to conventional purification measures, including distillation or chromatography or combined measures. Suitable distillation devices for the purification of the compounds of formulae (I) or (Ia), respectively, include, for example, distillation columns, such as tray columns optionally equipped with bubble cap trays, sieve plates, sieve trays, packages or filler materials, or spinning band columns, such as thin film evaporators, falling film evaporators, forced circulation evaporators, Sambay evaporators, etc. and combinations thereof.
- The starting compounds of the formulae (II) or (IIa) are known e.g. from
DE 2916418 ; they are commercially available or they can be prepared by analogy to the methods described inDE 2916418 . - GC-system: Agilent 5890 Series II;
GC-Column: 5CB-WAX-52CB (50 m (Length), 0.32 mm (ID), 1.2 µm (Film));
Temperature program: 40°C for 6 minutes, 40°C to until 250°C in 8°C/min. - 5.0 g (22.7 mmol) of the monoene of formula (IIa) and 0.3 g (1.15 mmol) RuCl3 in 25 ml 1,2-dichloromethane were placed into a 250 ml reaction flask, equipped with an 100 ml dropping funnel, an intensive condenser and a mechanical stirrer. Under vigorous stirring at 35°C, 75 ml of a 12.5 weight-% NaOCI-solution (126 mmol) in H2O charged with 1.5 g NaOH, were added. The pH of the reaction mixture was 14.0 at the start of the addition and dropped to pH 7.9 over time.
- The course of the oxidation reaction was followed by gas chromatographic analysis: After 2 hours, the conversion of the monoene (IIa) was 100% and the formation of the diketone of formula (Ia) 80% (GC area percent). After 3 hours, the formation of the diketone of formula (Ia) reached 94% (GC area percent).
- After completion of the reaction, the reaction mixture was allowed to cool down to room temperature and the organic phase was separated from the water phase. The water phase was washed with 1,2-dichloromethane. The ruthenium compound (catalyst) was separated from the organic phase by filtration and washed with 1,2-dichloromethane and water. The combined organic phases were dried over sodium sulfate and the solvent was removed under reduced pressure. An analysis of the reaction residual revealed 100% conversion of the monoene (IIa) and the formation of the wanted diketone of formula (Ia) of 95% (GC weight percent).
- 5.0 g (22.7 mmol) of the monoene of formula (IIa), 0.3 g (1.15 mmol) RuCl3 in 25 ml ethyl acetate and 25 ml of a Na2CO3/NaHCO3 buffer solution (pH 9,7) were placed into a 250 ml reaction flask, equipped with an 100 ml dropping funnel, an intensive condenser and a mechanical stirrer. Under vigorous stirring at 35°C, 75 ml of a 12.5 weight-% NaOCI-solution (126 mmol) in H2O charged with 1.5 g NaOH, were added. The pH of the reaction mixture was 10.8 at the start of the addition and dropped to pH 9.0 over time.
- The course of the oxidation reaction was followed by gas chromatographic analysis: After 2 hours, the conversion of the monoene (IIa) was 99.6% and the formation of the diketone of formula (Ia) 77.6% (GC area percent).
- After completion of the reaction, the reaction mixture was allowed to cool down to room temperature and the organic phase was separated from the water phase. The water phase was washed with ethyl acetate. The ruthenium compound (catalyst) was separated from the organic phase by filtration and washed with ethyl acetate and water. The combined organic phases were dried over sodium sulfate and the solvent was removed under reduced pressure. An analysis of the reaction residual revealed 100% conversion of the monoene (IIa) and the formation of the wanted diketone of formula (Ia) of 83.5% (GC weight percent).
- 5.0 g (22.7 mmol) of the monoene of formula (IIa) and 0.3 g (1.15 mmol) RuCl3 in 25 ml ethyl acetate were placed into a 250 ml reaction flask, equipped with an 100 ml dropping funnel, an intensive condenser and a mechanical stirrer. Under vigorous stirring at 35°C, 75 ml of a 12.5 weight-% NaOCI-solution (126 mmol) in H2O charged with 1.5 g NaOH, were added. The pH of the reaction mixture was 14.0 at the start of the addition and dropped to pH 7.6 over time.
- The course of the oxidation reaction was followed by gas chromatographic analysis: After 2 hours, the conversion of the monoene (IIa) was 100% and the formation of the diketone of formula (Ia) 66.7% (GC area percent).
- After completion of the reaction, the reaction mixture was allowed to cool down to room temperature and the organic phase was separated from the water phase. The water phase was washed with ethyl acetate. The ruthenium compound (catalyst) was separated from the organic phase by filtration and washed with ethyl acetate and water. The combined organic phases were dried over sodium sulfate and the solvent was removed under reduced pressure. An analysis of the reaction residual revealed 100 % conversion of the monoene (IIa) and the formation of the wanted diketone of formula (Ia) of 75.8% (GC weight percent).
- 5.0 g (22.7 mmol) of the monoene of formula (IIa), 0.3 g (1.15 mmol) RuCl3 in 25 ml MTBE and 25 ml of a Na2CO3/NaHCO3 buffer solution (pH 9,7) were placed into a 250 ml reaction flask, equipped with an 100 ml dropping funnel, an intensive condenser and a mechanical stirrer. Under vigorous stirring at 35°C, 75 ml of a 12.5 weight-% NaOCI-solution (126 mmol) in H2O charged with 1.5 g NaOH, were added. The pH of the reaction mixture was 12.7 over the course of the reaction. The course of the oxidation reaction was followed by gas chromatographic analysis. The total reaction time was 5 hours.
- After completion of the reaction, the reaction mixture was allowed to cool down to room temperature and the organic phase was separated from the water phase. The water phase was washed with MTBE. The ruthenium compound (catalyst) was separated from the organic phase by filtration and washed with MTBE and water. The combined organic phases were dried over sodium sulfate and the solvent was removed under reduced pressure. An analysis of the reaction residual revealed 100% conversion of the monoene (IIa) and the formation of the wanted diketone of formula (Ia) of 66.3% (GC weight percent).
- 5.0 g (22.7 mmol) of the monoene of formula (IIa) and 0.3 g (1.15 mmol) RuCl3 in 25 ml MTBE were placed into a 250 ml reaction flask, equipped with an 100 ml dropping funnel, an intensive condenser and a mechanical stirrer. Under vigorous stirring at 35°C, 75 ml of a 12.5 weight-% NaOCI-solution (126 mmol) in H2O charged with 1.5 g NaOH, were added. The pH of the reaction mixture was 9.4 over the course of the reaction. The course of the oxidation reaction was followed by gas chromatographic analysis. The total reaction time was 5 hours.
- After completion of the reaction, the reaction mixture was allowed to cool down to room temperature and the organic phase was separated from the water phase. The water phase was washed with MTBE. The ruthenium compound (catalyst) was separated from the organic phase by filtration and washed with MTBE and water. The combined organic phases were dried over sodium sulfate and the solvent was removed under reduced pressure. An analysis of the reaction residual revealed 100% conversion of the monoene (IIa) and the formation of the wanted diketone of formula (Ia) of 93.6% (GC weight percent).
- 89.5 g (0.40 mol) of the monoene of formula (IIa) and 5.8 g (23 mmol) RuCl3 in 500 ml MTBE were placed into a 2.5 l H=D reactor equipped with an 1 l dropping funnel, an intensive condenser and a 3-fold cross-arm stirrer (400 rpm). Under vigorous stirring at 35°C, 1.0 l of a 13.4 weight-% NaOCI-solution in H2O (1.80 mol), charged with 26.5 g NaOH (0.66 mol), were added. Following this, the reaction was run at 35°C for additional 10 hours.
- The course of the oxidation reaction was followed by gas chromatographic analysis: After 5 hours, the conversion of the monoene (IIa) was 83% and the formation of the diketone of formula (Ia) 72% (GC area percent). After 10 hours, the conversion of the monoene (IIa) was 100% and the formation of the diketone of formula (Ia) 91% (GC area percent).
- After completion of the reaction, the reaction mixture was allowed to cool down to room temperature and the organic phase was separated from the water phase. The water phase was washed with MTBE. The organic phase was first washed with 250 ml of a 20 weight-% solution of NaOH in water followed by 250 ml of water. The ruthenium compound (catalyst) was separated from the organic phase by filtration and washed with MTBE and water. After this washing step, the ruthenium compound (catalyst) was dried at 50°C for 2 hours and directly applied to the next oxidation reaction (vide example 7).
- The combined organic phases were dried over sodium sulfate and the solvent was removed under reduced pressure. 120.8 g of residual were obtained. An analysis of the residual revealed complete conversion of the monoene (IIa) and 76.7% of the wanted diketone (92.6 g, 0.367 mol, 91.7% yield).
- 89.5 g (0.40 mol) of the monoene of formula (IIa) and 5.9 g of recovered ruthenium compound (catalyst) from example 6 in 500 ml MTBE were placed into a 2,51 H=D - reactor equipped with an 1 l dropping funnel, an intensive condenser and a 3-fold cross-arm stirrer (400 rpm). Under vigorous stirring at 35°C, 1.0 l of a 13.4 weight-% NaOCI-solution in H2O (1.80 mol), charged with 26.5 g NaOH (0.66 mol), were added. Following this, the reaction was run at 35°C for additional 10 hours.
- The course of the oxidation reaction was followed by gas chromatographic analysis: After 5 hours, the conversion of the monoene (IIa) was 85% and the formation of the diketone of formula (Ia) 74% (GC area percent). After 10 hours, the conversion of the monoene (IIa) was 100% and the formation of the diketone of formula (Ia) 89% (GC area percent).
- After completion of the reaction, the reaction mixture was allowed to cool down to room temperature and the organic phase was separated from the water phase. The water phase was washed with MTBE. The organic phase was first washed with 250 ml of a 20 weight-% solution of NaOH in water followed by 250 ml of water. The ruthenium compound (catalyst) was separated from the organic phase by filtration and washed with MTBE and water. After this washing step, the ruthenium compound (catalyst) was dried at 50°C for 2 hours.
- The combined organic phases were dried over sodium sulfate and the solvent was removed under reduced pressure. 102.3 g of residual were obtained. An analysis of the residual revealed complete conversion of the monoene (IIa) and 89% of the wanted diketone (91.0 g, 0.361 mol, 90.3% yield).
Claims (14)
- A process for preparing a macrocyclic diketone compound of the formula (I), which comprises the oxidation of a bicycloolefine compound of the formula (II) with an oxidizing agent,A is (CH2)n with n being an integer from 2 to 12, where two hydrogen atoms may be replaced by C1-C4-alkyl or two hydrogen atoms, which are bound to adjacent carbon atoms may be replaced by a fused 5- or 6-membered saturated carbocycle;B is (CH2)m with m being 1 or 2, where 1 or 2 hydrogen atoms may be replaced by C1-C4-alkyl,where the oxidizing agent comprises a catalytic amount of a ruthenium compound and a co-oxidizing agent selected from selected from oxyanions of chlorine.
- The process of claim 1, where the total amount of the ruthenium compound in the reaction mixture, calculated based on the number of ruthenium atoms, is in the range of from 0.001 to 0.2 mol per 1 mol of compound of formula (II).
- The process of either claims 1 or 2, where the ruthenium compound is selected from ruthenium oxides, ruthenates, perruthenates, ruthenium halides, ruthenium nitrates and mixtures thereof.
- The process of any one of the preceding claims, where the total amount of the co-oxidizing agent used in the oxidation is in the range of from 2 to 10 mol per 1 mol of compound of formula (II), calculated as oxygen equivalent.
- The process of any one of the preceding claims, where the co-oxidizing agent is selected from hypochlorites.
- The process of any one of the preceding claims, where the pH of the reaction mixture is maintained in the range of from 7 to 14 during the oxidation of the compound of formula (II).
- The process of claim 6, where the maintenance of the pH is achieved by adding an aqueous buffer solution, comprising at least one buffering agent, having a pKa-value in the range of from 8 to 12, to the reaction mixture.
- The process of any one of the preceding claims, where the co-oxidizing agent is added to the reaction mixture in the form of an alkaline aqueous solution, having a pH of at least pH 10.
- The process of any one of the preceding claims, where the co-oxidizing agent is added continuously to the reaction mixture during the oxidation of the compound of formula (II).
- The process of any one of the preceding claims, where the molar ratio of the co-oxidizing agent to the ruthenium compound, which are applied to the reaction mixture, is in the range of from 10 : 1 to 10000 : 1.
- The process of any one of the preceding claims, where the oxidation of the compound of formula (II) is performed in the presence of an organic solvent or an organic solvent mixture.
- The process of any one of the preceding claims, where, after completion of the oxidation of the compound of formula (II), the ruthenium compound is recovered from the reaction mixture for further reuse.
- The process of any one of the preceding claims, where the compound of formula (I) is 3-methylcyclopentadecane-1,5-dione and the compound of formula (II) is 14-methylbicyclo[10.3.0]pentadecen[1(12)].
- The process of any of claims 1 to 12, where the compound of formula (I) is cyclopentadecane-1,5-dione and the compound of formula (II) is bicyclo[10.3.0]pentadecen[1(12)].
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PCT/EP2016/061221 WO2016184948A1 (en) | 2015-05-20 | 2016-05-19 | Process for preparing a macrocyclic diketone |
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EP (1) | EP3297983B1 (en) |
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ES2806203T3 (en) | 2015-06-03 | 2021-02-16 | Basf Se | 3-Methylcyclopentadecan-1,5-dione preparation procedure |
EP3170828A1 (en) * | 2015-11-23 | 2017-05-24 | Basf Se | Method for the preparation of compounds with 16-oxabicyclo [10.3.1] pentadecen scaffold and their secondary products |
EP3816297A1 (en) | 2016-02-19 | 2021-05-05 | Basf Se | Biocatalytic cyclising polyunsaturated carboxylic acid compounds |
CN109195959B (en) | 2016-05-31 | 2023-08-18 | 巴斯夫欧洲公司 | Tetrahydropyranyl lower alkyl esters and preparation using ketene compounds |
MX2019000664A (en) | 2016-07-15 | 2019-05-20 | Basf Se | Preparation of 14-methyl-16-oxabicyclo[10.3.1]pentadecenes from 3-methyl-1,5-cyclopentadecanedione. |
EP3649134B1 (en) | 2017-11-01 | 2021-07-21 | Firmenich SA | Process for preparing bicyclic enolether |
CN113166167A (en) | 2019-04-15 | 2021-07-23 | 弗门尼舍有限公司 | Process for preparing bicycloalkenol ethers |
CA3189779A1 (en) | 2020-08-10 | 2022-02-17 | E. I. Du Pont De Nemours And Company | Compositions and methods for enhancing resistance to northern leaf blight in maize |
WO2022115524A2 (en) | 2020-11-24 | 2022-06-02 | AgBiome, Inc. | Pesticidal genes and methods of use |
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CH513791A (en) | 1966-12-08 | 1971-10-15 | Firmenich & Cie | Preparing macrocyclic ketones |
CH519454A (en) | 1966-02-08 | 1972-02-29 | Firmenich & Cie | Preparing macrocyclic ketones |
CH503680A (en) * | 1966-12-08 | 1971-02-28 | Firmenich & Cie | Process for the preparation of macrocyclic ketones |
DE2916418A1 (en) | 1979-04-23 | 1980-11-06 | Basf Ag | 14-Methyl-bi:cyclo-10,3,0-pentadecene-1,2-muscone precursor prepn. - by alkylating cyclo:dodecanone with allyl halide, ozonising cyclising, conversion to bi:cyclic alcohol, dehydration and opt. isomerisation |
US4340753A (en) * | 1980-09-02 | 1982-07-20 | General Electric Company | Method for making keto acids and dione cyclics obtained therefrom |
JPS61289056A (en) | 1985-06-14 | 1986-12-19 | Agency Of Ind Science & Technol | Production of glutaric acid |
CN102786398A (en) | 2012-08-30 | 2012-11-21 | 新乡医学院 | Economic environment-friendly large-scale production technology for high-purity muscone |
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